The objective of the work described here is to study the biochemical composition and the topographical distribution of components involved in the potential dependent regulation of sodium conductance by excitable membranes. The venoms of two species of scorpion, Centuroides sculpturatus and Leiurus quinquestriatus, have been shown to specifically alter processes associated with sodium activation and sodium inactivation, respectively. The neurotoxin components have been isolated from these venoms. The precise physiological activity of each of these neurotoxins will be determined by voltage clamp experiments performed on frog Ranvier node. The interaction of each of the radiolabeled scorpion neurotoxins with a variety of excitable and non-excitable tissues will be monitored. Binding specificity and kinetics will be assayed under a range of experimental conditions. In other studies the neurotoxins, convalently linked to agarose beads, will serve as affinity reagents in affinity chromatography procedures. This technique, coupled with standard methodologies, should allow the isolation of membrane components associated with sodium activation and sodium inactivation from electroplax tissue of Electrophorus electricus. A biochemical characterization of these components will be carried out. In other experiments, the density and distribution of toxin specific sodium channel components in the membrane of neuron and muscle lines will be monitored as a function of morphological differentiation in cell culture. The effect of trophic interactions between various nerve and $ muscle cell lines on the density and distribution parameters will be studied.